Piperidine → HCID 60134503, compound

HRID 2061051Notes

Reaction equation

HRID 2061051 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:18])([CH3:17])[CH2:13][C:14]([OH:16])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>CN(C=O)C>[CH3:17][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH2:13][C:14](=[O:16])[N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)[CH3:18]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 682631,1'-CarbonyldiimidazoleHCID 145510073-(((Benzyloxy)carbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 60134503HCID 60134503, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-(benzyloxycarbonylamino)-3-methylbutanoic acid (11.8 g, 46.8 mmol) in DMF (100 mL) was added CDI (7.60 g, 1 equiv, 46.8 mmol) in one portion and stirred at room temperature for 2 h. Piperidine (9.27 mL, 2 equiv, 93.6 mmol) was added and the reaction was left to stir for 17 h. The solvent was removed on a rotovap and the residue was dissolved into a mixture of ethyl acetate (300 mL) and water (100 mL). The organic layer was separated and washed with saturated NaHCO3 solution (2×150 mL), 1 N HCl solution (150 mL) and brine (150 mL). It was dried over anhydrous MgSO4, filtered and concentrated to an oil. The crude material was purified on an ISCO system using a 220 g column and ethyl acetate and hexanes as eluent. The desired fractions were collected and concentrated to a colorless oil (8.84 g, 60%). 1H NMR (CDCl3, 400 MHz): δ 1.45 (s, 6H), 1.48-1.57 (m, 4H), 1.60-1.66 (m, 2H), 3.40-3.44 (m, 2H), 3.52-3.58 (m, 2H), 5.04 (s, 2H), 6.15 (s, 1H), 7.27-7.37 (m, 5H). LRMS (ESI+) for C18H26N2O3 (318.2); Found: 319 (MH+).

Workup

  1. waitthe reaction was left
  2. stirringto stir for 17 h
  3. customThe solvent was removed on a rotovap
  4. dissolutionthe residue was dissolved into a mixture of ethyl acetate (300 mL) and water (100 mL)
  5. customThe organic layer was separated
  6. washwashed with saturated NaHCO3 solution (2×150 mL), 1 N HCl solution (150 mL) and brine (150 mL)
  7. dry with materialIt was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe crude material was purified on an ISCO system
  11. customThe desired fractions were collected
  12. concentrationconcentrated to a colorless oil (8.84 g, 60%)

Sources & evidence

ORD record
ord-2e1b64e9b0d4499d975ae65ccd18eb95
Source dataset
uspto-grants-2012_10
Patent number
US08278482B2

Reaction notes

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